2-(Di-tert-butylphosphino)biphenyl → (S)-1,4-di(t-butoxycarbonyl)-2-(4-((R)-3-hydroxy pyrrolidino)phenyl)piperazine

HRID 1784679Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11][CH2:10][N:9]2[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[CH:4][CH:3]=1.[NH:28]1[CH2:32][CH2:31][C@@H:30]([OH:33])[CH2:29]1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+]>C(O)(C)(C)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C>[C:24]([O:23][C:21]([N:9]1[CH2:10][CH2:11][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:13][C@@H:8]1[C:5]1[CH:6]=[CH:7][C:2]([N:28]2[CH2:32][CH2:31][C@@H:30]([OH:33])[CH2:29]2)=[CH:3][CH:4]=1)=[O:22])([CH3:27])([CH3:26])[CH3:25]

Participants

Conditions

Temperature: 90 °C

Procedure

A suspension of (S)-2-(4-bromophenyl)-1,4-di(t-butoxycarbonyl) piperazine (1.33 g, 3.00 mmol), (R)-3-pyrrolidinol (520 mg, 4.20 mmol), palladium acetate (27 mg, 0.12 mmol), 2-(di-t-butylphosphino)biphenyl (72 mg, 0.24 mmol), and sodium t-butoxide (808 mg, 8.41 mmol) in tert-butanol (20 mL) was heated at 90° C. for 3.5 h. After dilution with ethyl acetate, the resulting mixture was passed through a Celite column. The filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography eluting 10-50% ethyl acetate-hexane to afford (S)-1,4-di-(t-butoxycarbonyl)-2-(4-((R)-3-hydroxypyrrolidino) phenyl)piperazine (733 mg, 54.5%) as a yellow foam.

Workup

concentrationThe filtrate was concentrated in vacuo
customthe residue was purified by silica gel column chromatography
washeluting 10-50% ethyl acetate-hexane

Sources & evidence

ORD record: ord-1a2856f551e44886a69872cb3f08fc44
Source dataset: uspto-grants-2009_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07504411B2

Reaction notes

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